tbuckley/cabot-search huggingface dataset:
Fungal exposome, human health, and unmet needs: A 2022 update with special focus on allergy
Authors: Joana Vitte, Moïse Michel, Andrei Malinovschi, Marco Caminati, Adeyinka Odebode, Isabella Annesi‐Maesano, Davide Paolo Caimmi, Carole Cassagne, Pascal Demoly, Enrico Heffler, Estelle Menu, Bright I. Nwaru, Youssouf Sereme, Stéphane Ranque, Monika Raulf, Wojciech Feleszko, Christer Janson, Carmen Galán
Journal: Allergy (2022)

Abstract Humans inhale, ingest, and touch thousands of fungi each day. The ubiquity and diversity of the fungal kingdom, reflected by its complex taxonomy, are in sharp contrast with our scarce knowledge about its distribution, pathogenic effects, and effective interventions at the environmental and individual levels. Here, we present an overview of salient features of fungi as permanent players of the human exposome and key determinants of human health, through the lens of fungal allergy and other fungal hypersensitivity reactions. Improved understanding of the fungal exposome sheds new light on the epidemiology of fungal‐related hypersensitivity diseases, their immunological substratum, the currently available methods, and biomarkers for environmental and medical fungi. Unmet needs are described and potential approaches are highlighted as perspectives.
Three new founder mutations in Chinese patients with Nagashima-type palmoplantar keratoderma
Authors: Juan Liu, Zhiming Chen, Linghan Hu, Zhongya Song, Ran Mo, Lemuel Shui-Lun Tsang, Yihe Liu, Xin Huang, Zhuoqing Gong, Ruiyu Xiang, Zhimiao Lin, Yong Yang
Journal: British Journal of Dermatology (2022)
Immunogenicity and safety of a fourth COVID-19 vaccination in rituximab-treated patients: an open-label extension study
Authors: Daniel Mrak, Elisabeth Simader, Daniela Sieghart, Peter Mandl, Helga Radner, Thomas Perkmann, Helmuth Haslacher, Margareta Mayer, Maximilian Koblischke, Philipp Hofer, Lisa Göschl, Felix Kartnig, Thomas Deimel, Andreas Kerschbaumer, Thomas Hummel, Barbara Kornek, Renate Thalhammer, Karin Stiasny, Stefan Winkler, Josef S Smolen, Judith H Aberle, Daniel Aletaha, Leonhard X Heinz, Michael Bonelli
Journal: Annals of the Rheumatic Diseases (2022)

Patients under rituximab therapy are at high risk for a severe COVID-19 disease course. Humoral immune responses to SARS-CoV-2 vaccination are vastly diminished in B-cell-depleted patients, even after a third vaccine dose. However, it remains unclear whether these patients benefit from a fourth vaccination and whether continued rituximab therapy affects antibody development.In this open-label extension trial, 37 rituximab-treated patients who received a third dose with either a vector or mRNA-based vaccine were vaccinated a fourth time with an mRNA-based vaccine (mRNA-1273 or BNT162b2). Key endpoints included the humoral and cellular immune response as well as safety after a fourth vaccination.The number of patients who seroconverted increased from 12/36 (33%) to 21/36 (58%) following the fourth COVID-19 vaccination. In patients with detectable antibodies to the spike protein's receptor-binding domain (median: 8.0 binding antibody units (BAU)/mL (quartiles: 0.4; 13.8)), elevated levels were observed after the fourth vaccination (134.0 BAU/mL (quartiles: 25.5; 1026.0)). Seroconversion and antibody increase were strongly diminished in patients who received rituximab treatment between the third and the fourth vaccination. The cellular immune response declined 12 weeks after the third vaccination, but could only be slightly enhanced by a fourth vaccination. No unexpected safety signals were detected, one serious adverse event not related to vaccination occurred.A fourth vaccine dose is immunogenic in a fraction of rituximab-treated patients. Continuation of rituximab treatment reduced humoral immune response, suggesting that rituximab affects a second booster vaccination. It might therefore be considered to postpone rituximab treatment in clinically stable patients.2021-002348-57.
Novel prime-boost immune-based therapy inhibiting both hepatitis B and D virus infections
Authors: Rani Burm, Panagiota Maravelia, Gustaf Ahlen, Sandra Ciesek, Noelia Caro Perez, Anna Pasetto, Stephan Urban, Freya Van Houtte, Lieven Verhoye, Heiner Wedemeyer, Magnus Johansson, Lars Frelin, Matti Sällberg, Philip Meuleman
Journal: Gut (2022)

Objective Chronic HBV/HDV infections are a major cause of liver cancer. Current treatments can only rarely eliminate HBV and HDV. Our previously developed preS1-HDAg immunotherapy could induce neutralising antibodies to HBV in vivo and raise HBV/HDV-specific T-cells. Here, we further investigate if a heterologous prime-boost strategy can circumvent T-cell tolerance and preclude HDV superinfection in vivo. Design A DNA prime-protein boost strategy was evaluated for immunogenicity in mice and rabbits. Its ability to circumvent T-cell tolerance was assessed in immunocompetent hepatitis B surface antigen (HBsAg)-transgenic mice. Neutralisation of HBV and HDV was evaluated both in vitro and in immunodeficient human-liver chimeric mice upon adoptive transfer. Results The prime-boost strategy elicits robust HBV/HDV-specific T-cells and preS1-antibodies that can effectively prevent HBV and HDV (co-)infection in vitro and in vivo. In a mouse model representing the chronic HBsAg carrier state, active immunisation primes high levels of preS1-antibodies and HDAg-specific T-cells. Moreover, transfer of vaccine-induced antibodies completely protects HBV-infected human-liver chimeric mice from HDV superinfection. Conclusion The herein described preS1-HDAg immunotherapy is shown to be immunogenic and vaccine-induced antibodies are highly effective at preventing HBV and HDV (super)infection both in vitro and in vivo. Our vaccine can complement current and future therapies for the control of chronic HBV and HDV infection.
RETRACTED ARTICLE: The LINC00623/NAT10 signaling axis promotes pancreatic cancer progression by remodeling ac4C modification of mRNA
Authors: Zengyu Feng, Kexian Li, Kai Qin, Juyong Liang, Minmin Shi, Yang Ma, Shiwei Zhao, Huaiyu Liang, Dongni Han, Baiyong Shen, Chenghong Peng, Hao Chen, Lingxi Jiang
Journal: Journal of Hematology & Oncology (2022)

Abstract Background Although a substantial increase in the survival of patients with other cancers has been observed in recent decades, pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest diseases. No effective screening approach exists. Methods Differential exosomal long noncoding RNAs (lncRNAs) isolated from the serum of patients with PDAC and healthy individuals were profiled to screen for potential markers in liquid biopsies. The functions of LINC00623 in PDAC cell proliferation, migration and invasion were confirmed through in vivo and in vitro assays. RNA pulldown, RNA immunoprecipitation (RIP) and coimmunoprecipitation (Co-IP) assays and rescue experiments were performed to explore the molecular mechanisms of the LINC00623/NAT10 signaling axis in PDAC progression. Results A novel lncRNA, LINC00623, was identified, and its diagnostic value was confirmed, as it could discriminate patients with PDAC from patients with benign pancreatic neoplasms and healthy individuals. Moreover, LINC00623 was shown to promote the tumorigenicity and migratory capacity of PDAC cells in vitro and in vivo. Mechanistically, LINC00623 bound to N-acetyltransferase 10 (NAT10) and blocked its ubiquitination-dependent degradation by recruiting the deubiquitinase USP39. As a key regulator of N4-acetylcytidine (ac4C) modification of mRNA, NAT10 was demonstrated to maintain the stability of oncogenic mRNAs and promote their translation efficiency through ac4C modification. Conclusions Our data revealed the role of LINC00623/NAT10 signaling axis in PDAC progression, showing that it is a potential biomarker and therapeutic target for PDAC.
Immune checkpoint modulators in cancer immunotherapy: recent advances and emerging concepts
Authors: Yuchen Wang, Hao Zhang, Chao Liu, Zeyu Wang, Wantao Wu, Nan Zhang, Longbo Zhang, Jason Hu, Peng Luo, Jian Zhang, Zaoqu Liu, Yun Peng, Zhixiong Liu, Lanhua Tang, Quan Cheng
Journal: Journal of Hematology & Oncology (2022)

Abstract The discovery of immune checkpoint inhibitors (ICIs) has now been universally acknowledged as a significant breakthrough in tumor therapy after the targeted treatment of checkpoint molecules: anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on several cancer types achieved satisfying results. However, there are still quite a lot of patients suffering from severe side effects and ineffective treatment outcomes. Although the current ICI therapy is far from satisfying, a series of novel immune checkpoint molecules with remarkable preclinical and clinical benefits are being widely investigated, like the V-domain Ig suppressor of T cell activation (VISTA), which can also be called PD-1 homolog (PD-1H), and ectonucleotidases: CD39, CD73, and CD38, which belong to the ribosyl cyclase family, etc. In this review, we systematically summarized and discussed these molecules' biological structures, molecular features, and the corresponding targeted drugs, aiming to help the in-depth understanding of immune checkpoint molecules and promote the clinical practice of ICI therapy.
High-dimensional investigation of the cerebrospinal fluid to explore and monitor CNS immune responses
Authors: Michael Heming, Anna-Lena Börsch, Heinz Wiendl, Gerd Meyer zu Hörste
Journal: Genome Medicine (2022)

The cerebrospinal fluid (CSF) features a unique immune cell composition and is in constant contact with the brain borders, thus permitting insights into the brain to diagnose and monitor diseases. Recently, the meninges, which are filled with CSF, were identified as a neuroimmunological interface, highlighting the potential of exploring central nervous system (CNS) immunity by studying CNS border compartments. Here, we summarize how single-cell transcriptomics of such border compartments advance our understanding of neurological diseases, the challenges that remain, and what opportunities novel multi-omic methods offer. Single-cell transcriptomics studies have detected cytotoxic CD4
Loss-of-function variants in<i>SAT1</i>cause X-linked childhood-onset systemic lupus erythematosus
Authors: Lingxiao Xu, Jian Zhao, Qing Sun, Xue Xu, Lei Wang, Ting Liu, Yunjuan Wu, Jingfeng Zhu, Linyu Geng, Yun Deng, Alexander Awgulewitsch, Diane L Kamen, Jim C Oates, Prithvi Raj, Edward K Wakeland, R Hal Scofield, Joel M Guthridge, Judith A James, Bevra H Hahn, Deborah K McCurdy, Fang Wang, Miaojia Zhang, Wenfeng Tan, Gary S Gilkeson, Betty P Tsao
Journal: Annals of the Rheumatic Diseases (2022)

Families that contain multiple siblings affected with childhood onset of systemic lupus erythematosus (SLE) likely have strong genetic predispositions. We performed whole exome sequencing (WES) to identify familial rare risk variants and to assess their effects in lupus.
Correlates and Consequences of an Acute Change in eGFR in Response to the SGLT2 Inhibitor Dapagliflozin in Patients with CKD
Authors: Niels Jongs, Glenn M. Chertow, Tom Greene, John J.V. McMurray, Anna Maria Langkilde, Ricardo Correa-Rotter, Naoki Kashihara, Peter Rossing, C. David Sjöström, Bergur V. Stefánsson, Robert D. Toto, David C. Wheeler, Hiddo J.L. Heerspink
Journal: Journal of the American Society of Nephrology (2022)

Dapagliflozin reduces kidney failure risk in patients with CKD but can result in a reversible acute reduction in eGFR upon treatment initiation. Determinants of this eGFR reduction and its associations with efficacy and safety outcomes are unknown.The DAPA-CKD trial randomized 4304 adults with CKD and albuminuria to once-daily dapagliflozin 10 mg or placebo, added to standard care. We prespecified an analysis comparing the effects of dapagliflozin among patients who experienced relative reductions in eGFR (>10% or >0%-10%) or an increase in eGFR from baseline to 2 weeks and assessed long-term efficacy and safety thereafter.A total of 4157 (96.6%) patients had eGFR data available at baseline and at 2 weeks. In the dapagliflozin and placebo groups, 1026 (49.4%) and 494 (23.7%), respectively, experienced an acute reduction in eGFR >10%. Among patients receiving dapagliflozin, those with an acute reduction in eGFR >10% experienced a long-term eGFR decline of -1.58 ml/min per 1.73 m2 per year compared with -2.44 and -2.48 ml/min per 1.73 m2 per year among those experiencing a less pronounced reduction or increase in eGFR, respectively (P-interaction=0.05). In the placebo group, long-term eGFR decline was -3.27, -3.84, and -3.77 ml/min per 1.73 m2 per year for acute eGFR reduction subgroups of >10%, >0%-10%, or increase in eGFR (P-interaction=0.48). Rates of serious adverse events and adverse events of special interest in patients randomized to dapagliflozin were unrelated to the acute eGFR change.Among patients with CKD and albuminuria treated with dapagliflozin, an acute reduction in eGFR (from baseline to 2 weeks) is not associated with higher rates of CKD progression.Clinical Trial registration number: A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease (Dapa-CKD) NCT03036150.
Durable protection against the SARS-CoV-2 Omicron variant is induced by an adjuvanted subunit vaccine
Authors: Prabhu S. Arunachalam, Yupeng Feng, Usama Ashraf, Mengyun Hu, Alexandra C. Walls, Venkata Viswanadh Edara, Veronika I. Zarnitsyna, Pyone Pyone Aye, Nadia Golden, Marcos C. Miranda, Kristyn W. M. Green, Breanna M. Threeton, Nicholas J. Maness, Brandon J. Beddingfield, Rudolf P. Bohm, Sarah E. Scheuermann, Kelly Goff, Jason Dufour, Kasi Russell-Lodrigue, Elizabeth Kepl, Brooke Fiala, Samuel Wrenn, Rashmi Ravichandran, Daniel Ellis, Lauren Carter, Kenneth Rogers, Lisa M. Shirreff, Douglas E. Ferrell, Nihar R. Deb Adhikary, Jane Fontenot, Holly L. Hammond, Matthew Frieman, Alba Grifoni, Alessandro Sette, Derek T. O’Hagan, Robbert Van Der Most, Rino Rappuoli, Francois Villinger, Harry Kleanthous, Jay Rappaport, Mehul S. Suthar, David Veesler, Taia T. Wang, Neil P. King, Bali Pulendran
Journal: Science Translational Medicine (2022)

Despite the remarkable efficacy of COVID-19 vaccines, waning immunity and the emergence of SARS-CoV-2 variants such as Omicron represents a global health challenge. Here, we present data from a study in nonhuman primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine comprising the receptor binding domain of the ancestral strain (RBD-Wu) on the I53-50 nanoparticle adjuvanted with AS03, which was recently authorized for use in individuals 18 years or older. Vaccination induced neutralizing antibody (nAb) titers that were maintained at high concentrations for at least 1 year after two doses, with a pseudovirus nAb geometric mean titer (GMT) of 1978 and a live virus nAb GMT of 1331 against the ancestral strain but not against the Omicron BA.1 variant. However, a booster dose at 6 to 12 months with RBD-Wu or RBD-β (RBD from the Beta variant) displayed on I53-50 elicited high neutralizing titers against the ancestral and Omicron variants. In addition, we observed persistent neutralization titers against a panel of sarbecoviruses, including SARS-CoV. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Vaccination resulted in protection against Omicron infection in the lung and suppression of viral burden in the nares at 6 weeks after the final booster immunization. Even at 6 months after vaccination, we observed protection in the lung and rapid control of virus in the nares. These results highlight the durable and cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine.
Management and outcomes of pregnant women admitted to intensive care unit for severe pneumonia related to SARS-CoV-2 infection: the multicenter and international COVIDPREG study
Authors: Edwige Péju, Félicie Belicard, Stein Silva, Sami Hraiech, Benoît Painvin, Toufik Kamel, Arnaud W. Thille, Antoine Goury, David Grimaldi, Boris Jung, Michael Piagnerelli, Hadrien Winiszewski, Merce Jourdain, Mathieu Jozwiak, Laurent Argaud, Cécile Aubron, Nicolas Bèle, François Beloncle, Pierre-Marie Bertrand, Laetitia Bodenes, Filippo Boroli, Belaid Bouhemad, Lucie Braconnier, William Buffieres, Cédric Darreau, Jean Dellamonica, Stephan Ehrmann, Mélanie Faure, Sébastien Gibot, Claudine Gniadek, Marine Goudelin, Pierre-Alban Guenier, Christophe Guitton, Etienne Haussaire, Julie Helms, Matthieu Jamme, Michel Kaidomar, Jean-Baptiste Lascarrou, Christophe Le Terrier, Julien Maizel, Ferhat Meziani, Jean-Paul Mira, Lucas Morand, Grégoire Muller, Benjamin Pequignot, Gaël Piton, Jérôme Pugin, Alexandre Robert, Michael Siino, Bertrand Souweine, Mattieu Stanowski, Fabienne Tamion, Nicolas Terzi, Guillaume Thiery
Journal: Intensive Care Medicine (2022)
Differences in Phosphate and Parathyroid Hormone Concentrations over the Day among Patients on Hemodialysis
Authors: Charles Ginsberg, Lindsay M. Miller, Norma Ofsthun, Lorien S. Dalrymple, Joachim H. Ix
Journal: Journal of the American Society of Nephrology (2022)

Elevated serum phosphate and parathyroid hormone (PTH) concentrations are associated with cardiovascular events, bone disease, and mortality in patients on maintenance hemodialysis. Although circadian changes are known in people with CKD, it is unknown whether differences occur in these parameters over the course of a day in people receiving hemodialysis.We used clinical data from Fresenius Medical Care US dialysis clinics to determine how the time of day when measurements were collected (hemodialysis treatment start time) may be associated with serum phosphate and PTH concentrations. We used harmonic regression to assess these associations while accounting for demographic data and treatment parameters.A total of 96,319 patients receiving maintenance hemodialysis were included in this analysis. Patients had a mean age of 64±14 years, 43% were women, and dialysis start times ranged from 3:00 am to 7:59 pm. The mean serum phosphate concentration was 5.2±1.5 mg/dl, and the median PTH was 351 pg/ml (interquartile range [IQR], 214-547). In fully adjusted models, serum phosphate had a nadir at 11:00 am of 4.97 (IQR, 4.94-5.01) mg/dl and a peak at 7:00 pm of 5.56 (IQR, 5.50-5.62) mg/dl. Serum PTH had a nadir at 9:00 am of 385 (IQR, 375-395) pg/ml and a peak at 7:00 pm of 530 (IQR, 516-547) pg/ml.Among patients receiving maintenance hemodialysis, concentrations of PTH and phosphate before a dialysis session vary with the time of day that these values are measured. Consideration of whether these values were obtained at peak or nadir times of the day may be important in treatment decisions.
Sex Differences in Age-Related Loss of Kidney Function
Authors: Toralf Melsom, Jon Viljar Norvik, Inger Therese Enoksen, Vidar Stefansson, Ulla Dorte Mathisen, Ole Martin Fuskevåg, Trond G. Jenssen, Marit D. Solbu, Bjørn O. Eriksen
Journal: Journal of the American Society of Nephrology (2022)

CKD is more prevalent in women, but more men receive kidney replacement therapy for kidney failure. This apparent contradiction is not well understood.We investigated sex differences in the loss of kidney function and whether any sex disparities could be explained by comorbidity or CKD risk factors. In the Renal Iohexol Clearance Survey (RENIS) in northern Europe, we recruited 1837 persons (53% women, aged 50-62 years) representative of the general population and without self-reported diabetes, CKD, or cardiovascular disease. Participants' GFR was measured by plasma iohexol clearance in 2007-2009 (n=1627), 2013-2015 (n=1324), and 2018-2020 (n=1384). At each study visit, healthy persons were defined as having no major chronic diseases or risk factors for CKD. We used generalized additive mixed models to assess age- and sex-specific GFR decline rates.Women had a lower GFR than men at baseline (mean [SD], 90.0 [14.0] versus 98.0 [13.7] ml/min per 1.73 m2; P<0.001). The mean GFR change rate was -0.96 (95% confidence interval [CI], -0.88 to -1.04) ml/min per 1.73 m2 per year in women and -1.20 (95% confidence interval [CI], -1.12 to -1.28) in men. Although the relationship between age and GFR was very close to linear in women, it was curvilinear in men, with steeper GFR slopes at older ages (nonlinear effect; P<0.001). Healthy persons had a slower GFR decline, but health status did not explain the sex difference in the GFR decline.Among middle-aged and elderly individuals in the general population, decline in the mean GFR in women was slower than in men, independent of health status.
Is daily supervised buprenorphine-naloxone dosing necessary?
Journal: BMJ (2022)

Is daily supervised buprenorphine-naloxone dosing necessary?We introduced some errors into this article by Robert Kleinman and colleagues (BMJ 2022;378:e071467, doi:) at proof stage.A reference was omitted from the end of the first paragraph, the description of buprenorphine's effect on respiratory depression was inaccurate, and some of the confidence intervals were reversed in the section "Unsupervised dosing is safe and effective."The online version has been corrected.
The diagnostic and triage accuracy of digital and online symptom checker tools: a systematic review
Authors: William Wallace, Calvin Chan, Swathikan Chidambaram, Lydia Hanna, Fahad Mujtaba Iqbal, Amish Acharya, Pasha Normahani, Hutan Ashrafian, Sheraz R. Markar, Viknesh Sounderajah, Ara Darzi
Journal: npj Digital Medicine (2022)

Abstract Digital and online symptom checkers are an increasingly adopted class of health technologies that enable patients to input their symptoms and biodata to produce a set of likely diagnoses and associated triage advice. However, concerns regarding the accuracy and safety of these symptom checkers have been raised. This systematic review evaluates the accuracy of symptom checkers in providing diagnoses and appropriate triage advice. MEDLINE and Web of Science were searched for studies that used either real or simulated patients to evaluate online or digital symptom checkers. The primary outcomes were the diagnostic and triage accuracy of the symptom checkers. The QUADAS-2 tool was used to assess study quality. Of the 177 studies retrieved, 10 studies met the inclusion criteria. Researchers evaluated the accuracy of symptom checkers using a variety of medical conditions, including ophthalmological conditions, inflammatory arthritides and HIV. A total of 50% of the studies recruited real patients, while the remainder used simulated cases. The diagnostic accuracy of the primary diagnosis was low across included studies (range: 19–37.9%) and varied between individual symptom checkers, despite consistent symptom data input. Triage accuracy (range: 48.8–90.1%) was typically higher than diagnostic accuracy. Overall, the diagnostic and triage accuracy of symptom checkers are variable and of low accuracy. Given the increasing push towards adopting this class of technologies across numerous health systems, this study demonstrates that reliance upon symptom checkers could pose significant patient safety hazards. Large-scale primary studies, based upon real-world data, are warranted to demonstrate the adequate performance of these technologies in a manner that is non-inferior to current best practices. Moreover, an urgent assessment of how these systems are regulated and implemented is required.
Discovery of novel predisposing coding and noncoding variants in familial Hodgkin lymphoma
Authors: Jamie E. Flerlage, Jason R. Myers, Jamie L. Maciaszek, Ninad Oak, Sara R. Rashkin, Yawei Hui, Yong-Dong Wang, Wenan Chen, Gang Wu, Ti-Cheng Chang, Kayla Hamilton, Saima S. Tithi, Lynn R. Goldin, Melissa Rotunno, Neil Caporaso, Aurélie Vogt, Deborah Flamish, Kathleen Wyatt, Jia Liu, Margaret Tucker, Christopher N. Hahn, Anna L. Brown, Hamish S. Scott, Charles Mullighan, Kim E. Nichols, Monika L. Metzger, Mary L. McMaster, Jun J. Yang, Evadnie Rampersaud
Journal: Blood (2022)